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' to listin widen the gene al" h ad n ee Patented Dec. 22, 1953 PRocEss rromrrnnsemolnsczr OXIDATION- smirrmmw on AcE'rYL mo GAMMA-i branammo hmir, s ai dfli i YY- bio-Drawing:- Anplication-Novemherfl, 19.48, Serial No. 5858 My invention relates to a" process for the fi 'i direct? oxidation-splitting. of .acetyle'hicigam'mae glycols to yield, immediately; prodiictsuseful" arid convenient vto the. synthesis ofjalpha; hydroxy acids, the salts of alpha-hydroxy acids; the .lactides of' alpha-whydroxy. acids, a'n'g. the esters of alpha-hydroxy acids f Acetylenic gamma-game have heretofore been ,subjcted ito oxidation-.splififiin bia variety Qf means, includingz.

I. The directfr oxidation, of a. acetylifiicr gamma-glycols by such materials as .acid-fpo sium permanganate systems; alkalin'epotaiss permanganate. systems; .acid-dichromate salt systems; Fentons Reagent (30% hytifo'geii peroxidewsolutions plus ferrousisulfgte oi-tcop per sulfate as; a catalyst)"; an' dflhorieagueoiis hydrogen peroxide. solutions the presence or osmium tetroxide; alias perEqu'atioii 1 to yield" aliaha-hy'droxy acids as the desired prodii'cts" of the reactions.

(1') 0zonnlysesof acetylenie: gammaag lyegls resu tr ing in the formation of thesozo ide deriva es of-:the :starting; a'cetylenic gamma-igl-ycois; igllowed ebywater-promoted dec mpos tion H -the the'rprocess sequenc r-h de c ibed is entiilefi:

methods forpromot n the dir ct x daiieri splitting of acetylenic gamma-giycolsw II-. i-The fi di t* d t or e l-t l n -9. yle ic am ae ycqls ia h ox dat on spli ieg: of their di-esterderivatives unqer the "influence o Such agents as acid-p ta s um ermanganat systemsr l alin t s umpe an anatewe terns; racicl-di hr mate l s em:;--Fni9; Reagent; and.- a variety of other chemical o gi dizirig, reagents,- allfias per Equationhz... to yieigl alpha-tester acids as the desiredr products of the s elafnisr gol. 260 340 7 III." The midi-rest cxidation of acetylehic gamma=glycois-- via t1i! oxidatiomsplitting :of their-etherdefivatii es by sue Hai irgf th is state'q' the hature' or thepri'o a as re 'a di he "dir i methods of accomiiIislii'ng"the ting of acetylenic gamma-glycol'si'it" is tl'i proper and petinent 'to devote a few brief critical comments to theaccomplishments of the prior art.

The direct oxidation-splitting of acetylenic gamma ly ols-as ou l ned un t m 11 gs? 10p 11 5 by which the"direct oxidation of "may ammae l p siha z'be n char r bi ed with the h cosfofth I fit 1;;-

iilbybd" i P mo mime ri acw orisfhave r' glycols to comparatively few commercial applications.

The methods listed under item III above, like those included under item II, are generally endowed with high reaction efliciency characteristics. In this case, however, the restricted use of the methods falling under item 111 is attributable not only to the high cost of the oxidation reagents employed, but also to the limited versatility of the alpha-alkoxy acids thus produced as regards their conversion to other chemically useful materials.

In'the equations given above, the symbol R in any given formula is to be taken to mean either a hydrogen atom or an alkyl radical. The symbol R is to be understood to mean an allryl radical exclusively. The use of numerical subscripts in connection with any of the formulae given herein is intended to generalize the equations for the instances where non-symmetrical acetylenic gamma-glycols are encountered. The asymmetry may consist of different alkyl radicals on both sides of the carbon linked to the acetylenic group; or, the asymmetry may involve non-identical groups attached to the acetylenically-bound carbons; or, combinations of the above-mentioned circumstances. This system of notation is continued below. V

Having thus reviewed the prior art, I now pass to a presentation of my invention as regards the oxidation-splitting of acetylenic gamma-glycols. The generalized description of my invention may be divided into three component parts;

A. A step in which the acetylenic gamma-glycols answering the generalized formula,

are reacted with pyroboric acid to create the diborate ester derivative of the given glycol; while acetylenic gamma-glycols answering to the generalized formula,

R: lli'z R1(:J- -4-11,

are converted to their di-acetate ester derivatives. B. A step in which the di-ester derivatives of the starting acetylenic gamma-glycols are subjected to oxidation-splitting via the treatment of the di-ester derivatives obtained as per item A with gaseous oxygen under the conditions of temperature which will be described below, employing either boric acid or phosphoric acid or silicic acid as the catalyst for this operation. 0. Individual procedures for the conversion of the immediate product of the oxidation-splitting operation to free alpha-hydroxy acids, the salts of alpha-hydroxy acids, the lactides of alphahydroxy acids, and the esters of alpha-hydroxy acids.

The function served by the step in which the starting acetylenic gamma-glycol is converted to one or the other of the above-mentioned diester derivatives thereof is to localize the oxidation reaction and to render it specific to the oxidation of the triple-bond.

There are many satisfactory methods by which the respective di-ester derivatives mentioned above may be prepared.

' Thus the di-acetoxy ester may be obtained by (1) the reaction of an acetylenic gamma-glycol with acetic anhydride in the presence of sodium acetate; (2) the reaction of ketene with an acetylenic gamma-glycol; and (3) the direct reaction of an acetylenic gamma-glycol with glacial acetic acid in the presence of a third component such as xylol, in which process sequence the xylol serves to effect the pseudo-azeotropic distillation of the water-of-reaction.

-Where the di-borate ester of an acetylenic gamma-glycol is desired, again it is possible to use any of a number of satisfactory techniques. These may include (i) a direct reaction between boric anhydride and the acetylenic gammaglycol, in the presence of a solvent where the demands of temperature control impose the requirement of good agitation of the reaction system and the reactants-mixture per se does not possess the desired fluid properties; (2) a direct reaction between the acetylenic gamma-glycol and pyroboric acid, sometimes in the presence of a solvent for the reasons cited in the previous echnique; and (3) a reaction between the acetylenic gamma-glycol and boric acid in the presence of a third and inert solvent such as toluol or xylol under the conditions of a pseudo-azeotropic distillation of the water from the reaction system.

In the preferred embodiment of my invention, the di-acetoxy derivatives of acetylenic gammaglycols are prepared by the action of acetic anhydride on the acetylenic gamma-glycols under the influence of sodium acetate as a catalyst at a temperature for the reaction ranging between C; and 140 0., depending upon the glycol at handand its stability characteristics in the presence of acetic acid and acetic anhydride itself.

The resultant reaction system is then subjected to a fractionation operation for the purposes of isolating the di-acetoxy derivative of the acetylenic gamma glycol.

In the preferred embodiment of my invention, where the :di-borate ester of an acetylenic gamma-glycol is prepared, the given gammaglycol is dissolved in a solvent such as benzene, toluene, or xylol and is reacted with pyroboric acid under the conditions of a gradual addition of the pyroboric acid powder to the solution of the acetylenic gamma-glycol, while maintaining vigorous agitation and a reaction temperature lying in the range between 30 C. and C.

The detailed procedures implicit in the aforementioned preferred methods for the prepara tion, respectively, of the di-acetoxy and the diborate ester derivatives of acetylenic gammaglycols, and the unit operations which connect these steps with the subsequent steps of my invention are set forth generally in the illustrative examples appearing later herein.

Where the oxidation-splitting operation is carried out on the di-borate ester derivative of an acetylenic gamma-glycol, no measures are employed for the isolation of the ester other than the removal of the solvent medium in which the reaction was executed. This is carried out under such vacuum conditions that at no time during the removal of the solvent mediumby the vacuum stripping operation is a temperature of 30 C;

735?, 5 i' -::$-1+.5-I-I\-'si. gm-g' mfz exceeded. When in accordance with the rule at down above, the di-acetoxy derivative of an acetylenic glycol is employed, the dif-ester is isolated from the reaction mass fonthe bestiresults.

"we "retina-s where the di-borate ester derivative of an acetylenic glycol is to be subjected to an oxidation-splitting etieeit ie bp e id lQy-Pwev of the borate ester formati6n,vihere boricanhydride or pyroboric acid are employed in the di-ester synthesis, or the eggcess of boric acid used in the third-named metho d above, 'fnay PE utilized as the'catalyst-for theoxidation-splittmg operation. Wheregthe di-acetoxy derivative of an acetylenic glycol is to beprocessed, between one and fifteen percent of 100% phosphoric acid,

loa sedpn theyveight oi di;es terg b eing processed, is esi ie ato d a .t io. Enrol kco {k oose.-

'55 spofid a'-' (L4 abat attest. H p

. -splitting .phenom nQ iQn iacetylenic. gammazs t st getensionwoittheyiew pli d i. 1. ,to; various instanc s t: nqnw. yminetr lenictga mma-dir ompo unds'willb' mm atelmappar-ent a, P 40, According to thelhest time asia result oiimyoreseqreheslth aii of the reactions, thieh talge place e rifluence of oxygen passage through the reaction niass are those set forth under Equations} through 8 4 5 fQrthQcase Pf the di-alcetoxy compounds, and Equations 9 through 1"3"for the "cas'e'of the diborate; compounds. A

In other words, the evidence collected by me refiearohc tend i t .fr afiinisit ii- Ffom th' sit ati'dnfthe addition of the molecular oxygen to form a peroxidegwhich later rearranges itself to a di-keto forn may-Joe visualized. Thislentire concept is :1 projected inEqiiation 4. According to Equation 5fthe' reaction bettfeen oxygen and phosphoric acid to yield a peroxide rafdical' and a dih'ydrogen phosphate radical is postulated. The splitting of -the di-keto form under the influence of the peroxide and the di-hydrogen phosphate radicals cally then generally, from the modern knowledge of the action of alkyl peroxides in related reactions. The reaction projected in Equation 8 between the alpha-acetoxy acid (produced in accordance with Equation '7) with the di-hydrogen phosphate compound (produced according to Equation 6) in which the regeneration of the acid catalyst and the yielding of another molecule of the acid anhydride is presented, flows quite logically from the previous development of the probable reaction mechanics involved in the oxidation-splitting phenomenon as accomplished by me.

In Equations 9 through 13, the probable reaction mechanics involved in the oxidation-splitting of acetylenic gamma-di-borate esters is projected for the case where'boric acid .is employed -as the oxidation-splitting catalyst.

In other words, in both instances the direct product of the reaction between the di-esters set forth above and oxygen, under'the conditions generally described above, is an alpha-ester acid anhydride.

. The third phase of my invention, namely, the methods by which I convert the alpha-acetoxy acid anhydride or the alpha-borate acid anhydride which I obtain as the direct product of the oxidation-splitting operation to the various end products listed by me in the: statement of my invention, in each case involves the transformation of the alpha-ester anhydride to the lactide of the homologous alpha-hydroxy acids to which they are related. The conversion of alphaacetoxy acid anhydrides to the indicated lactide forms is accomplished in the following manner:

' To the reaction mass resulting from the performance'of the oxidation-splitting operation on the di-acetoxy ester derivative of an acetylenic gamma-glycol, one adds approximately one and one-quarter times the stoichiometric requirement of water to decompose the anhydride, and thereby yield the free alpha-acetoxy acid. This reaction is illustrated in Equation 14.

i r r r ACOCC E I IOECOAO HOH AcOC- C (14) I IRI I This reaction is usually instantaneous, even when The reaction mass resulting from the operation in Equation 14 is thentransferred to a reactor flask provided with agitation and equipped with a Bidwell-Sterling adapter which connects the reactor flask with a vertical condenser. To

the reaction mass present in the reactor flask,

there is added that quantity of xylol or toluol which is consistent with maintaining the highest possible temperature for the ensuing'refluxing operation which avoids the serious inception or accen 8 the side-reactions set forth under Equations 16 'andll:

t a r t M00 HAc-l.(i1l is it on tlim 0H (Where R is an alkyl group) o R" o- R{ H o o 2R'|CR'+2CQ 11 UR c-o \R' a The reaction set'forth in Equation l6,-'\vhich consists of thesplitting out of a molecule of acetic acid from the structure of the alpha-acetoxy acid to yield an unsaturated derivative acid, is'a phenomenon with an energy-of-activation which depends on the particular alpha-acetoxy acid being processed. The temperatures, therefore; at which thisphenomenon will take place for a given alpha-acetoxy acid is peculiar to that alphaacetoxy acid. The degradation reaction set forth'under Equation 1'7 similarly shows a varialactide product.

tion from lactide to lactide; and, consequently. no maximum temperature range can be specified for the lactide form-ation reaction which would broadly hold for all lactides.

The receptacle portion of the Bidwell-sterling adapter is then fiiled with such a quantity of 'xylol or toluol that the droppingof condensate from the vertical condenser causes an overflow of xylcl from the receptacle portion of the adapter to the reactor flask. Maintaining vigorous agitation, one is able to maintain the reaction mass in the flask under reflux conditions. The toluolor xylol-acetic acid-water distillate from the flask passes from the reactor flask to the vertical condenser, where it is condensed and dropped to the receptacle portion of the Bidwell- Sterling adapter. The water-acetic acid mixture settles to the bottom of the Bidwell-Sterling adapter receptacle, while the xylol component of the distillate becomes an upper layer. The receptacle portion of the Bidwell-Sterling adapter is tapped at such intervals as assures the maintaining of the originally stipulated maximum reaction temperature. This operation is continued until no further acetic acid is taken over. The lactide of the homologous alpha-hydroxy acid to the starting alpha-acetoxy acid will then be found in solution in xylol in the reactor flask. The xylol is then driven on, generally under vacuum stripping'conditions, to obtain the crude The formation of the lactide from the alpha-acetoxy acid starting reactant is carried out in the presence of the phosphoric acid present in the reaction mass as a result of its original incorporation in the oxidation-splitting phase of my invention. The phosphoric acid acts, in the case of the lactide formation, again in the role of a catalyst.

The conversion of alpha-borate acid anhydrides, where these are involved in my invention, to the lactides of their homologous alpha-hydroxy acid forms is, with the exception of a few elements of detailed procedure, accomplished by the same general methods mentioned above in connection with the conversion of alpha-acetoxy acid anhydrides to lactides.

The procedures, and the reactions involved, where they differ from the instances provided by the above-described conversion of alpha-acetoxy it will be observed that the treatment of alpha-borate *acid anhydride with water results not only in the convers'iont'o the ireeiacid form; Y}

but "also in thehydrolysisof the" borate group to yield twomols of' theal-pha-hydroxy acid shown on the'right-hand side'of Equation-18w a 'Depending upon the lability' of the so produced the phenomenon-set forth-under Equ ion =19,-- LAP.- HULK i zm ion 31303 3H2O [Hts ooh 13+ lg-m /s j cooling of the reaction mass during the Water promoted decomposition of the alphaeborate acid anhydride may-become necessary. Since alphahy'droxy acids'vary in theirlability to the con-- ditions'invoked by theformation of the complex set forth under Equation 19, it is notpossible to prescribe hardand-fast rules regarding the tem peratures which must be maintained during :the l water promotedidecomposition reaction. Since boric acid is presentiin the reaction mass resulting from the hydrolysis operation in'sharp...

excess 'over' the stoichi'ometric-irequirements of Equation 19, the reaction to produce theicoma:

pl'e'X-st forth under Equation 19is rather complete. The formation of the lactideiof the alpha-.- hydroxy acidproduced in accordanceiwith: Equation 20 therefore presupposes the destructio'nsoitHe compIeXT -The destruction of the-'complex is accomplished by the reacting of "the-mixture re-e' sulting fromthe addition of a slurry of calcium hydroxide to the reaction "mass resultingrfromthen hydrolysis jperatiomf' I y.

s t. a fiif'i )1 s? 2K 2% OH H C O o. (Ii cm A 20% slurry of calcium hydroxide, providing calcium hydroxide in tsharpcaexcess-aofthe stoic'hiometric relationshipsinvolved in Equation 21; is employed forthis-operation, a rig,

the

alpha' 'hydroxyacids to "destructionathrougha forniation of the powerful-acids :i'ESdlliing-fi01i'1-- basis for the separation of the calcium salt of the lehaehyclroxysacia512cm th aer assoqf ca ci hyd o de emp e fa st a reland-her to:

The reaction filtration I operation, following. which the: calcium;

salt of.- the alpha-,hydroxyy acid.will be iound solution in sthe; .filtrate. -'I 'he-calciuna iborateyre sul ingi-irom theabo e: en io dfih a im r011 eration, may-be treated with 36% hydrochloric acideatroom temperatures to recoverithe origi nallyremployed borie-acid forre use. The fil trate, containing the calc iumsalt of the alpha m ydroxyfi idnifi; ac d t d smo em e atu e withany reasonab e 1 3 8 iover st i hi me requirementof:phosphori ac dtq yi ldtthe V haa ydroxy aqi r u l um ph ha p cesseswofjphosphoric acid in theorder of 5% t 10% ;--.of the expected eld; oflactidej' Will grv thebest results.--;-; a The thus processed filtrate is then subjected to treatment in,anpapparatussset-up completely identical to that describeol --.for the ,converson f the-salpha-ac t x "faci s to wlac i e a ver temperature :for; the refluxing operation; intt Whi H'i E D Si IiQ wi h ne'gemmxi iongqi t degradation reaction setgorth und atio 2 V w (22 The crude lactides which are thus obtained by each -ofthe sets -of operations described.abovev may be isolatedin pure form from their accomu-li panying impurities by extraction ot-"thel final. residues in--the-reactor =fiaskmemberssaof thev above-described standard laboratory equipmentr. set-ups with such solvents as diethyl ether; after which the purelactideis obtained by lvacuum=- evaporation of the ether solvent.

The conversionof-thecrude lactides, or the purified 'lactides (Whichever may prove to be more convenient in -any -given-instance) to the. esters of-alpha-hydroxy 'acids (by the :well; known processes oftransesterification), to free. alpha-hydroxy;-acids -(by the conversion of the. lactide to a salt of the alpha-hydroxy-acids byte. saponificationaction; followed by I an acidulationi of theysalt and, an extraction of; the free alpha hydroxy acid thus -obtained )-,--and -to the salts of alpha -hydroxy acids (by the s aponificatio n -of the lactide1)- are procedures well-known to-those art v. v. I Those skilled inthe art will readily appreciate thatth-e broad-ranges of processing conditions-i which I have set f orth above flevv from the broad scope of applicability -of my; invention. 1 have Z however; in each important-processingcondition; given; the principles which'guide the selection oi the optimum conditions for the carrying out of any specificapplication of -my invention.-

'The advantages ofiered-flcy my-in-vention over thepr-ior art are thei-followingz- .1 21. 1'. I-n*-contradistinction" tow/all methods previouslyaoifered vfor-the fdirect and[or-;?indirect' V oxidationssplitting 0Lacetylenicgainrna glycols,

1 h dec m s ion fthec mw 11 described above will be obtained when optimum conditions are observed, depending upon the particular acetylenic gamma-glycol being processed.

2. In. contradistinction to all methods previously proposed in the prior art for the oxidation-splitting of acetylenic gamma-glycols, re-- gardless of whether these means have been of the direct or indirect type, the reagent material used in my invention, namely oxygen, will demonstrate a greater applicability commercially to the extent that gaseous oxygen is available at a lower cost than are any of the oxidation agents previously employed in the prior art. Taken into account with this factor, one must also consider the fact that the weight of oxygen demanded per unit of end-product lactide realized is lower than the weight of any of the oxidation reagents prescribed in the prior art per unit of final product achieved on a purely theoretical basis. Combining this factor with the higher yield efliciencies achieved by me and the lower excesses of oxidation reagents required by me over those recommended by the prior art in the instances of the various oxidation agents employed by them, the oxidation-splitting of acetylenic gamma-glycols becomes an economically feasible operation in the synthesis of many low-cost and useful chemicals.

3. When the oxidation-splitting operation is performed on the di-borate ester derivative of the acetylenic gamma-glycol (in instances where I propose the use of the di-borate ester of the starting acetylenic gamma-glycol), my invention offers the particular advantages that the synthesis of free alpha-hydroxy acids, their salts,

their esters, and their lactides are placed within range of simple preparation without entailing a high cost of reagent materials in the preparation of a suitable di-ester for the oxidation-splitting operation. This follows from the above-mentioned technique for the recovery of the boric acid side-product of the alpha-borate acid anhydride hydrolysis, and the technique which is proposed in my second illustrative example for the preparation of pyroboric acid.

4. The fact that the alpha-acid anhydride intermediate product present in the reaction mass at the end ofthe oxidation-splitting operation may, by the procedures recommended above, be converted to the lactide of the respective expected alpha-hydroxy acid final product lends the syntheses proposed by me to the easy, rapid, and eflicient achievement of the esters and the calcium, sodium, and other salt derivatives of alphahydroxy acids.

Undoubtedly those skilled in the art will be capable of introducing many variants on the techniques proposed by me. Instances of such possible variations of the procedures I propose include the following:

a. The use of di-ester derivatives, other than the di-acetoxy derivative of the acetylenic gamma-glycol, in instances where the use of the di-acetoxy ester derivative is proposed, such as the di-propionoxy, etc., ester derivatives of any given acetylenic gamma-glycol. In this regard, the general purposes for which the di-acetoxy ester derivative of the starting acetylenic gammaglycol is used in connection with my methods of oxidation-splitting of the acetylenic triplebond is the vital factor, rather than the particular form of the di-ester derivative employed.

b. In instances where the di-borate ester derivative of a starting acetylenic gamma-glycol is employed, it is possible to substitute other in 1a organic ester derivatives such as the di-phos phate, the di-bisulfate, etc., ester derivatives. Here again, the main purposes served by the creation of the di-borate ester derivative which include the protection of the hydroxyl stations against direct oxidation, the obtaining of an alpha-ester product which will resist oxidation, and the achievement of a form which will be susceptible to immediate direct hydrolysis is the underlying principle involved.

0. Relative to the particular di-ester derivative of the starting acetylenic gamma-glycol employed, it is possible that in given instances, higher degrees of protection of the basic acetylenic gamma-glycol structure against degradation to di-vinyl acetylene structures may be obtained from the use of one di-ester derivative over another. Similarly, and following from this consideration, it is possible that the achieving of the additional protection of the basic acetylenic gamma-glycol structure from the side-reaction tendencies mentioned above may lend itself towards the use of higher temperatures for the oxidatiomsplitting operation, thereby permitting a more rapid achievement of the oxidation-splitting operation.

Since many possibilities are presented for the conversion of the immediate product of the oxidation-splittin operation as performed by my invention to the salts of alpha-hydroxy acids, free alpha-hydroxy acids, and the esters of alpha-hydroxy acids, it should be underscored that the methods or" converting the alpha-ester acid anhydrides which my method of performing the oxidation-splitting operation achieves, to the mentioned products which I propose, are illustrative rather than specific to the general invention here outlined.

Relative to the use of oxygen as the oxidizing agent, it is also possible, by sacrificing speed of reaction, to employ air in the place of the oxygen specified by me.

The following are illustrative examples of the application of my invention to the oxidationsplitting of acetylenic gamma-glycols to yield alpha-ester acid anhydrides as the direct product of the oxidation-splitting operation, with the indicated potentialities for conversion of the acid anhydride to the free alpha-hydroxy acids, the

lactides of the free alpha-hydroxy acids, the salts of the free alpha-hydroxy acids, and the esters of the free alpha-hydroxy acids.

Example 1.-T7ie synthesis of the lactide of lactic acid from 2,5-diol hatin -3 To a flask provided with agitation and connected by way of a Bidwell-Sterling adapter to a vertically mounted water-cooled condenser, 175 g. of boric acid and 1,350 cc. of xylol are added. The flask is then heated until reflux conditions are established. Vapors of xylol and water pass to the vertically mounted condenser, where they are condensed and dropped to the receptacle portion of the Bidwell-Sterling adapter. A collection of a two-phase distillate, of which the xylol is the upper layer and of which water is the lower layer, ensues. As the operation progresses, the receptacle portion of the Bidwell-Sterling adapter becomes filled with condensate, so that ultimately the continued passage of condensate to the receptacle causes the continuous overflow of the collected xylol upper layer to the flask. The receptacle portion of the adapter is tapped at suiiiciently frequent intervals to guarantee a height oi xylol layer in the receptacle consistent with constantly m yaa ettl. e:

. .a matelyfiflr ojthe e eld of di-borate ester derivative. aving thus removed the solvent m h e a yst ms: he temrieratutaoii i di-borate ester;,derivat i ve.is raised tallfl" C., and, maintainin the reaction mass temperature at llQFf C; for the entire period-of-fourand one-halihpurs,- 91.51.; of oxygen; referred to standard con ditions, are passed-into thesolution aver the alloted four and one-half hour reaction time. The reaction mass from the aforementioned processing procedure is then added to 40 cc. of water, while vigorously agitating the reaction system resulting from this addition. The alphaborate acid anhydride, obtained from the oxidation-splitting operation, is added to the water at the maximum rate which is consistent with the continued maintaining of a temperature of 0., under the conditions of an ice-water bath cooling of the reaction flask, for the entire duration of the addition sequence. To the thus obtained reaction system, a slurry of 450 g. of calcium hydroxide in 1.8 l. of water is added. This operation is also carried out under the conditions of a constantly maintained reaction temperature of 20 C. The reaction mass resulting from this operation is filtered, and the filtrate from this operation is processed in the following manner:

A charge of 237 g. of 50% phosphoric acid is added to the filtrate, while maintaining a reaction temperature not in excess of 40 C. Adding a quantity of xylol consistent with maintaining a refluxing temperature not in excess of 135 C. as a maximum condition to the thus obtained aqueous solution of lactic acid, a pseudo-azeotropic distillation of Water in an apparatus set-up completely identical to that described for the case of the conversion of boric acid to pyroboric acid is pursued until no further water is collected. The reaction mass then remaining in the reactor flask is taken up in diethyl ether, subjected to a filtration for the separation of all inorganic materials umis ri i z 14- s lut a .ot heproduc scare-1.. :1. a v dA.

ethereal s11;

a .i he; i. efficiency of 86% on the basis gi t 9;. expected yield from the starting a 11351 mmaegl q ls stpbtem siii This cmaterial is suitable fqrg the for niethyllac atnand othe1g,este onversion-flamesa ts 5 version to. laqtiaac d. i tsalf To a reaction system consisting ..of..200.-,g;. 0.1L.

hydrous sodium 'acetate,there is graduallyadde'ii while "the" hexin'e sodium" acetate. mixture. maintained at 105 0., 349g. of'acetic anhydrida, rhjniii obtained reached ystem" agitated at thesarne tempe atu e-rt;spends bf two' and on e-haljrf hours, tithe; conclusion of which; thefln l reactio'ri inass is'subjectedf-toa vacuum distilla "n'operationto" relive'tl i reactionm'ass of the" acetic acid'"product "of reaction and i the excess of acetic anhydride originally empwyea; The thus isolated df toxy'derivative crasdimetlriyl" 2,5: di61 'hexine-3Jrec'eives a' charge -of 20 of'10'0"% Y phosphoric. acid; The phosphoric; a'cid'fdi-acetexy ester istlien subjected to an? cation-emittingoperatmi 'einpioym a uniformly...

maintained reaction temperature of 145 111. in, m grain mariner reg-eras reactiontime, condition's'" of "agitation, and general). manner. of..- oxygen-input, as was described in Example 1. A wayiof or gea amduntin to 7 3.51.1. of;oxygen, referred t'fstandard conditions, ispnflss di through the. solution during the oxidation-151211115 ting operation. The alpha-acetoxy acid anhydri'de resulting from this operation is then proc; essed in the following manner:

To the acid anhydride, there is added 40 cc. of water, while a reaction temperature of C. as a maximum is maintained. Employing a standard laboratory distillation set-up, in which the efiiuent from the top of the distillation column passes by way of a Bidwell-Sterling adapter to a vertically mounted water-cooled condenser and maintaining the receptacle portion of the Bidwell-Sterling adapter charged at all times with a small layer of Water, a mixture of the decomposed acid anhydride and of toluol is subjected to refluxing under atmospheric pressure conditions. A suflicient amount of toluol is maintained in the reactor at all times, so that at no time during the progress of the lactide formation operation is a temperature of 135 C. exceeded. When no further acetic acid distills over from the reactor flask, the formation of the lactide of alpha-hydroxy isobutyric acid is complete. The isolation of the lactide in pure form again involves the taking up of the residue in the reactor flask in diethyl ether, the careful settling of the ethereal solution from the phosphoric acid sediment contained therein, and the final separation of the lactide by the vacuum stripping of the ether of solution under vacuum stripping conditions. In this manner, a yield of 221 g. of the lactide of alpha-hydroxy isobutyric acid, representing a yield efiiciency of on the basis of the theoretically expected yield from 15 2,5-dimethyl 2,5-diol hexine-B is obtained. The lactide in this instance is also capable of conversion to the methyl and other esters of alphahydroxy acid via a transesterification operation, and, by the same sequence of procedures as is proposed, of conversion to the salts of alphahydroxy isobutyric acid and free alpha-hydroxy isobutyric acid itself.

I claim:

1. In the indirect oxidation-splitting of acetylenic gamma-glycols in which an acetylenic gamma-glycol is converted to the corresponding di-ester and subjected to an oxidation-splitting operation, the improvement comprising incorporating an oxidation catalyst selected from the group consisting of phosphoric acid, boric acid, and silicic acid in the di-ester of the gamma glycol, introducing gaseous oxygen into the resulting mixture and thereby oxidizing the diester at the point of the acetylenic linkage and splitting the di-ester at said point, and mixing the resulting product with water to hydrolyze the resulting reaction product.

2. The process as claimed in claim 1 characterized in that the di-ester is oxidized at a temperature of from 80 to 200 C.

3. The process as claimed in claim 1 characterized in that said resulting reaction product is hydrolyzed at a temperature of from about 20 to 60 C.

4. The process as claimed in claim 1 characterized in that the hydrolyzing operation is effected in the presence of the oxidation catalyst, thereby producing a lactide having the same number of carbon atoms as the acetylenic gamma-glycol.

5. The process as claimed in claim 1 characterized in that the di-ester is an ester of an aliphatic acid.

6. The process of producing lactide products from organic di-esters of acetylenic gamma-glycols, comprising the steps of oxidizing a di-ester 16 of an acetylenic gamma-glycol with gaseous oxygen in the presence of an oxidation catalyst selected from the group consisting of phosphoric acid, boric acid, and silicic acid at a. temperature of from 80 to 200 C., thereby converting the di-ester to the corresponding alpha-ester acid anhydride, mixing the anhydride product with water i to efiect hydrolyzation thereof, mixing the water and anhydride at a temperature substantially below the oxidation temperature, azeotropically distilling an the water and regenerated organic acid from the hydrolyzed mixture in the presence of the oxidation catalyst, and thereafter separating the lactide product from the catalyst.

7. The process as claimed in claim 6 character ized in that the di-ester is an ester of acetic acid.

8. A process for the indirect oxidation-splitting of symmetrical acetylenic gamma-glycols for the production of lactides of alpha-hydroxy acids, which comprises converting an acetylenic gamma-glycol to an acetylenic gamma-di-ester derivative thereof, heating the resulting acetylenic gamma-di-ester derivative with substantially pure oxygen gas in the presence of phosphoric acid as an oxidation catalyst and oxidizing said derivative to split the di-ester derivative and prouce an alpha-ester acid anhydride product mixture, reacting the said product mixture containing the phosphoric acid with water and thereby converting the product to the alpha-ester acid derivative, thereafter refluxing the resulting mixture in the presence of water thereby converting said last-mentioned derivative to a lactide, and

recovering the resulting lactide product.

ABRAHAM BROTHMAN.

References Cited in the file of this patent UNITED STATES PATENTS Rosenblum Feb. 13, 1940 

1. IN THE INDIRECT OXIDATION-SPLITTING OF ACETYLENIC GAMMA-GLYCOLS IN WHICH AN ACETYLENIC GAMMA-GLYCOL IS CONVERTED TO THE CORRESPONDING DI-ESTER AND SUBJECTED TO AN OXIDATION-SPLITTING OPERATION, THE IMPROVEMENT COMPRISING INCORPORATING AN OXIDATION CATALYST SELECTED FROM THE GROUP CONSISTING OF PHOSPHORIC ACID, BORIC ACID, AND SILICIC ACID IN THE DI-ESTER OF THE GAMMAGLYCOL, INTRODUCING GASEOUS OXYGEN INTO THE RESULTING MIXTURE AND THEREBY OXIDIZING THE DIESTER AT THE POINT OF THE ACETYLENIC LINKAGE AND SPLITTING THE DI-ESTER AT SAID POINT, AND MIXING THE RESULTING PRODUCT WITH WATER TO HYDROLYZE THE RESULTING REACTION PRODUCT. 